Objectives To investigate the effects of simvastatin on membrane ionic currents in left ventricular myocytes of rabbit heart suffering from acute myocardial infarction （ AMI）, so as to explore the ionic mechanism of...Objectives To investigate the effects of simvastatin on membrane ionic currents in left ventricular myocytes of rabbit heart suffering from acute myocardial infarction （ AMI）, so as to explore the ionic mechanism of statin treatment for antiarrhythmia. Methods Forty-five New Zealand rabbits were randomly divided into three groups： AMI group, simvastatin intervention group （ Statin group） and sham-operated control group （CON）. Rabbits were infarcted by ligation of the left anterior descending coronary artery after administration of oral simvastatin 5 mg · kg^-1·d^-1 （Statin group） or placebo （AMI group） for 3 days. Single ventricular myocytes were isolated enzymatically from the epicardial zone of the infracted region 72 h later. Whole cell patch clamp technique was used to record membrane ionic currents, including sodium current （INa）, L-type calcium current （Ica-L） and transient outward potassium current （Ito）. Results （1） There was not significant difference in serum cholesterol concentration among three groups. （2） The peak INa current density （at -30 mV） was significantly decreased in AMI group （ -25.26±5.28, n = 13 ）, comparing with CON （ - 42. 78± 5.48, n = 16）, P 〈 0. 05, while it was significantly increased in Statin group （ - 39.83 ±5.65 pA/pF, n = 12） comparing with AMI group, P 〈0. 01 ; The peak Ica-L current density （ at 0 mV） was significantly decreased in AMI group （ -3. 43 ±0. 92 pA/pF, n = 13） comparing with CON （ -4. 56 ±1.01 pA/pF, n = 15）, P 〈0. 05, while it was significantly increased in Statin group （ -4. 18±0. 96 pA/pF, n = 12） comparing with AMI group, P 〈0. 05; The Ito current density （ at ＋ 60 mV） was significantly decreased in AMI group （ 11.41 ± 1.94 pA/pF, n = 13 ） comparing with CON （17.41 ±3.13 pA/pF, n = 15）, P 〈0. 01, while it was significantly increased in Statin group （16. 11 ± 2. 43 pA/pF, n = 14） comparing with AMI group, P 〈 0. 01. Conclusions AMI induces signific展开更多
Hydrogel patch-based stem cell transplantation and microenvironment-regulating drug delivery strategy is promising for the treatment of myocardial infarction(MI).However,the low retention of cells and drugs limits the...Hydrogel patch-based stem cell transplantation and microenvironment-regulating drug delivery strategy is promising for the treatment of myocardial infarction(MI).However,the low retention of cells and drugs limits their therapeutic efficacies.Here,we propose a prefixed sponge carpet strategy,that is,aldehyde-dextran sponge(ODS)loading anti-oxidative/autophagy-regulating molecular capsules of 2-hydroxy-β-cyclodextrin@resveratrol(HP-β-CD@Res)is first bonded to the rat’s heart via capillary removal of interfacial water from the tissue surface,and the subsequent Schiff base reaction between the aldehyde groups on ODS and amino groups on myocardium tissue.Then,an aqueous biocompatible hydrazided hyaluronic acid(HHA)solution encapsulating mesenchymal stem cells(MSCs)is impregnated into the anchored carpet to form HHA@ODS@HP-β-CD@Res hydrogel in situ via click reaction,thus prolonging the in vivo retention time of therapeutic drug and cells.Importantly,the HHA added to outer surface consumes the remaining aldehydes to contribute to nonsticky top surface,avoiding adhesion to other tissues.The embedded HP-β-CD@Res molecular capsules with antioxidant and autophagy regulation bioactivities can considerably improve cardiac microenvironment,reduce cardiomyocyte apoptosis,and enhance the survival of transplanted MSCs,thereby promoting cardiac repair by facilitating angiogenesis and reducing cardiac fibrosis.展开更多
文摘Objectives To investigate the effects of simvastatin on membrane ionic currents in left ventricular myocytes of rabbit heart suffering from acute myocardial infarction （ AMI）, so as to explore the ionic mechanism of statin treatment for antiarrhythmia. Methods Forty-five New Zealand rabbits were randomly divided into three groups： AMI group, simvastatin intervention group （ Statin group） and sham-operated control group （CON）. Rabbits were infarcted by ligation of the left anterior descending coronary artery after administration of oral simvastatin 5 mg · kg^-1·d^-1 （Statin group） or placebo （AMI group） for 3 days. Single ventricular myocytes were isolated enzymatically from the epicardial zone of the infracted region 72 h later. Whole cell patch clamp technique was used to record membrane ionic currents, including sodium current （INa）, L-type calcium current （Ica-L） and transient outward potassium current （Ito）. Results （1） There was not significant difference in serum cholesterol concentration among three groups. （2） The peak INa current density （at -30 mV） was significantly decreased in AMI group （ -25.26±5.28, n = 13 ）, comparing with CON （ - 42. 78± 5.48, n = 16）, P 〈 0. 05, while it was significantly increased in Statin group （ - 39.83 ±5.65 pA/pF, n = 12） comparing with AMI group, P 〈0. 01 ; The peak Ica-L current density （ at 0 mV） was significantly decreased in AMI group （ -3. 43 ±0. 92 pA/pF, n = 13） comparing with CON （ -4. 56 ±1.01 pA/pF, n = 15）, P 〈0. 05, while it was significantly increased in Statin group （ -4. 18±0. 96 pA/pF, n = 12） comparing with AMI group, P 〈0. 05; The Ito current density （ at ＋ 60 mV） was significantly decreased in AMI group （ 11.41 ± 1.94 pA/pF, n = 13 ） comparing with CON （17.41 ±3.13 pA/pF, n = 15）, P 〈0. 01, while it was significantly increased in Statin group （16. 11 ± 2. 43 pA/pF, n = 14） comparing with AMI group, P 〈 0. 01. Conclusions AMI induces signific
基金National Natural Science Foundation of China(Grant No.52233008,51733006)National Key Research and Development Program(Grant No.2018YFA0703100).
文摘Hydrogel patch-based stem cell transplantation and microenvironment-regulating drug delivery strategy is promising for the treatment of myocardial infarction(MI).However,the low retention of cells and drugs limits their therapeutic efficacies.Here,we propose a prefixed sponge carpet strategy,that is,aldehyde-dextran sponge(ODS)loading anti-oxidative/autophagy-regulating molecular capsules of 2-hydroxy-β-cyclodextrin@resveratrol(HP-β-CD@Res)is first bonded to the rat’s heart via capillary removal of interfacial water from the tissue surface,and the subsequent Schiff base reaction between the aldehyde groups on ODS and amino groups on myocardium tissue.Then,an aqueous biocompatible hydrazided hyaluronic acid(HHA)solution encapsulating mesenchymal stem cells(MSCs)is impregnated into the anchored carpet to form HHA@ODS@HP-β-CD@Res hydrogel in situ via click reaction,thus prolonging the in vivo retention time of therapeutic drug and cells.Importantly,the HHA added to outer surface consumes the remaining aldehydes to contribute to nonsticky top surface,avoiding adhesion to other tissues.The embedded HP-β-CD@Res molecular capsules with antioxidant and autophagy regulation bioactivities can considerably improve cardiac microenvironment,reduce cardiomyocyte apoptosis,and enhance the survival of transplanted MSCs,thereby promoting cardiac repair by facilitating angiogenesis and reducing cardiac fibrosis.
